Search agents

Biological systems produce an extremely wide variety of natural products. This ecological and genetic diversity offers researchers a vast index of compounds to search for innovative weed management agents. 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

CASSIS USPTO USPTO Office of Electronic Data Conversion and Dissemination CASSIS, the Classification and Search Support Information System of the USPTO, comprises three subfiles CASSIS/BIB, bibHographic information for utiHty patents from 1969 and for others from 1977 CASSIS/CLASS, USPTO classification by patent number of class/subclass CASSIS/ASSIST, iadex to U.S. Manual of Classification U.S. Manual of Classification, Class Definitions IPC, U.S. Classification Concordance Manual of Patent Examining Procedure Attorneys/ Agents Roster, etc... 

A novel approach to the problem of amiaoglycoside nephrotoxicity has been to search for compounds that can inhibit toxicity without compromising efficacy. A number of agents have been reported to reduce amiaoglycoside toxicity ia animal models the most extensively studied of these is sodium polyaspartate (103—107). 

Standard Mosquito Repellents. Since its initial report as a promising repellent in 1954, DEET has been considered the best all-around repellent having generally acceptable characteristics, despite a continuing search for a superior chemical. Improvements include many commercial products with added cosmetic agents that use slow release technology, such as the U.S. Armed Services slow release 35% DEET formulation (16). There were 35 EPA-registered repellent products in 1994 that contained only DEET under different trade names (2). DEET is present in 192 of the 212 products mentioned previously (2). 

In order to circumvent this problem, there has been significant activity directed toward the search for a less environmentally toxic and more selective oxidizing agent than chromium. For example, Hoechst has patented a process which uses organorhenium compounds. At a 75% conversion, a mixture of 86% of 2-methyl-l,4-naphthoquinone and 14% 6-methyl-l,4-naphthoquinone was obtained (60). Ceric sulfate (61) and electrochemistry (62,63) have also been used. 

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

The search for new antivkal agents is ongoing and extensive not all vimses have been included here, and new vimses pathogenic to humans will continue to be identified. Novel nucleosides as weU as nonnucleosidic compounds which possess greater potency and enzymic specificity for the future treatment of both acute and persistent human vkal infection will continue to be discovered. 

Agglomeration-Based Fine Coal Cleaning. Most recently a search for nonaqueous collectors or reagents for fine coal cleaning has been undertaken. A number of Hquids have been tested and found to be suitable as agglomeration agents. These include heavy oil. Freon, pentane, hexane, heptane, 2-methylbutane, methyl chloride, and Hquid carbon dioxide. 

While melamine is widely used in flexible foams as a fire-retardant, trichlorphenyl phosphate has been the preferred agent for use in rigid foams. However, the introduction of specifications stipulating halogen-free additives has led to a search for alternatives such as halogen-free phosphorus esters, red phosphorus and ammonium polyphosphate. 

By the turn of the century the theory of chemical mediation of physiologic responses had gained some currency. There ensued in some laboratories an intense search for endogenous chemical modifiers of bodily responses. The first such agent to be isolated from mammalian tissue was the ubiquitous hormone, epinephrine—at that time known as adrenaline. This compound has played an important role in pharmacology as well as in medicinal chemistry. 

The relatively low potency of aspirin in overcoming the symptoms of inflammatory diseases has led to a continuing search for new antiinflammatory agents. Although many more potent agents have been introduced to clinical practice, most of these elicit some side effects that limit their use. Derivatives of iv-aryl anthra-nillic acids have provided a series of quite effective antiinflammatory drugs, the so-called fenamic acids. 

The lack of oral activity of progesterone proper has already been mentioned. Even after the orally active 19-nor agents, which showed progestational activity, had been elaborated, the search continued for an orally active compound that contained the full pregnane nucleus (115). At the time such a compound would have had the economic advantage of sidestepping the then burdensome ring A aromatization reactions. 

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